Ovarian cancer is the fourth most frequent cause of cancer death among women in the United States. Of all females born in the United States, one of every 70 will develop ovarian cancer and one of every 100 will die from ovarian cancer. See, e.g., R. Young et al., in 1 Cancer: Principles & Practices of Oncology, at 1162 (3d ed. 1989)(V. DeVita, S. Hellman, and S. Rosenberg eds.). Similar statistics are reported for many European countries. Ovarian cancer is much more amenable to treatment if detected in its early stages, but is notoriously difficult to detect in its early stages.
The antigenic determinant designated CA125 is the current serum marker of choice for monitoring epithelial ovarian cancer at second look surgical surveillance procedures. CA125 is elevated in serum from 80-90% of ovarian cancer patients, but not in the remaining 10-20% even in the presence of bulky disease. See, e.g., R. Bast et al., N. Engl. J. Med. 309, 883-87 (1983). At second look surgical surveillance procedures, CA125 is elevated in 20% of patients (associated with a 96% positive predictive value for the presence of persistent disease), while as many as 50-60% of patients with normal CA125 levels have persistent ovarian cancer. See J. Berek et al., Obstet. Gynecol. 67, 685-89 (1986). Hence, there has long been a need for a means of monitoring epithelial ovarian cancer supplemental to CA125. Previous studies with potential new markers have, however, identified only 10-20% of patients with persistent disease who have normal CA125 levels.
Colon cancer is one of the most common internal malignancies in the United States, occurring in approximately 5% of the population. (See, e.g., Sugarbaker et al., Colorectal Cancer, In Cancer: Principles and Practices of Oncology at 795 (2d edition, 1985) (DeVita, Hellman & Rosenberg, eds.). The tumor marker carcinoembryonic antigen (CEA) is an antigen specific for adenocarcinomas of the digestive tract and is also elevated in cancers other than colon carcinoma. CEA has been found to be clinically useful in monitoring colon, pancreatic, gastric, lung and breast cancers. CEA is the current serum marker of choice for diagnosing colon cancer and for monitoring of patients after resection of colon cancer. CEA may also be elevated in several common benign conditions such as inflammatory bowel disease and diverticulitis, and is not therefore recommended for general screening of asymptomatic individuals for colon cancer. A significant increase in CEA after curative surgical resection of colon cancer is associated with disease recurrence, and is used to indicate the need for second-look surgery. Schneebaum et al., Dis. Colon Rectum, 36,810 (1993). However, from 30-60% of patients with recurrent colon cancer do not have measurable levels of CEA. Guadagni et al., Cancer, 72, 2098 (1993). Additional means supplemental to the use of CEA are need in screening, diagnosing and monitoring colon cancer.
The present invention arose from our ongoing efforts to develop new methods of monitoring and diagnosing ovarian, endometrial and colon cancer.